A multicenter, single-arm clinical study of evaluate the efficacy and safety of avapritinib as maintenance therapy following allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia patients with KIT mutation.
It has been reported that in patients with CBF-associated acute myeloid leukemia (CBF-AML), c-kit mutations occur preferentially in patients with core-binding factor ((8; 21) and inv(16) or t(16; 16) (referred to as inv(16)) rearrangements. However, c-KIT gene mutations, which occur more frequently in patients with CBF-AML, have an incidence of 10% to 45%, which in turn leads to relapse, suggesting a poor prognosis. Nearly 50% of AML patients with concomitant t(8;21) have the c-KIT-D816 mutation. Among AML patients with t(8; 21), patients with c-KIT D816 mutation had significantly shorter OS and EFS than those without this mutation. Avapritinib, is a novel inhibitor of KIT and PDGFRA-activating ring mutants and a potent and selective inhibitor of KIT D816V, and preclinical studies have demonstrated that compared to Midostauin, Avapritinib is 10-fold more potent against this mutant kinase was 10-fold more potent. A retrospective study \[ 14 \] analyzed the efficacy of Avapritinib in patients with t (8;21) AML with KIT mutations who failed allo-HSCT treatment. Among the 13 patients in the D816 mutation, 8 cases reduced RUNX1-RUNX1T1 transcript levels by ≥1 log after 1 month of treatment, and 3 cases turned negative. However, whether avapritinib is effective for maintenance therapy in CBF-AML patients who harbor KIT mutations is unknown. There is a lack of prospective, controlled studies to clarify the efficacy and safety of XPO1 inhibitor combined with venetoclax as maintenance therapy after allo-HSCTin patients with intermediate- to high-risk AML/MDS, especially those with out specific gene mutation which would be targeted with commerically available inhibitors. Therefore, this multicenter, single-arm study is designed to assess the efficacy and safety of avapritinib as maintenance therapy in CBF-AML patients who harbor KIT mutations after allo-HSCT, with the aim of providing a reference for clinical treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
47
After allo-HSCT, CBF-AML patients who have kit mutation would receive avapritinib for maintenance therapy.
Ruijin Hospital of Shanghai Jiaotong University
Shanghai, Shanghai Municipality, China
Cumulative incidence of relapse
disease relapse
Time frame: through study completion, an average of 2 year
Overall survival
death as a result of any causes
Time frame: through study completion, an average of 2 year
Non relapse mortality
death without disease progression or relapse
Time frame: through study completion, an average of 2 year
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